The present invention relates to a process for preparing 3-hydroxy-5-methylisoxazole, which process is carried out continuously, in part or in whole, and which has a number of practical advantages.
3-Hydroxy-5-methylisoxazole has the formula (I): ##STR1## It is used as an agricultural fungicide and has a remarkable activity, particularly against soil-borne diseases.
Japanese Patent Specifications (published for opposition) Nos. 48953/74 and 9675/77 disclose methods of preparing 3-hydroxy-5-methylisoxazole (I) from diketene (II) and an O-alkyl or O-aralkyl substituted hydroxylamine (III), as illustrated in the following reaction scheme: ##STR2## As shown in this reaction scheme, the reaction of diketene with the substituted hydroxylamine (III) gives an O-substituted acetoacetohydroxamic acid (IV). This acid (IV) is subjected to catalytic reduction followed by acidification or simply to acidification to remove the alkyl or aralkyl group represented by R and cyclise the compound, thus giving the desired 3-hydroxy-5-methylisoxazole.
Since the O-alkyl or O-aralkyl substituted hydroxylamine (III) is normally prepared from free hydroxylamine, it might appear logical from the above reaction scheme to use free hydroxylamine instead of the substituted hydroxylamine and thereby to omit the step of removing the alkyl or aralkyl group represented by R; this might be expected to give acetoacetohydroxamic acid (V) which would then cyclise to the desired 3-hydroxy-5-methylisoxazole. However, it has been established [Zhur. Obschei Khim. 20, 1858 (1950) and Chem. Pharm. Bull. 13, 248 (1965)] that the reaction of diketene with free hydroxylamine produces acetoacetic acid oxime (IX) and 3-methyl-2-isoxazolin-5-one (X). It is believed that these products are formed because the acetoacetohydroxamic acid (V) formed by the reaction is very unstable and quickly reacts with further hydroxylamine or with any nucleophilic agent present in the reaction system, as shown in the following reaction scheme: ##STR3##
Accordingly, it has been difficult hitherto to produce 3-hydroxy-5-methylisoxazole industrially by using diketene and free hydroxylamine as the starting materials.